The Slit family of migratory cues is secreted by midline cells, endothelial cells and cancer cells. They bind to a family of cell-surface transmembrane proteins, Roundabout (Robo), and act as repellants for axon guidance and neuronal migration, endogenous inhibitors for leukocyte chemotaxis and chemoattractants for vascular endothelial cells. To assess the pathological significance and to elucidate the underlying molecular mechanisms for Slit-Robo signaling in the growth and metastasis of tumors, we will investigate (1) the effect of Slit-Robo signaling in lymphangiogenesis and lymphatic metastasis, the pathological role of Slit2 in tumor angiogenesis and growth and (2) the effect of Slit-Robo signaling on canonical Wnt signaling. We believe that these studies will not only deepen our understanding of the molecular mechanisms involved in tumor growth and metastasis, but also facilitate the use of Slit2 and Robo1 as the novel molecular targets for diagnosis and treatment of cancers. PUBLIC HEALTH RELEVANCE: Our study on Slit-Robo signaling in tumor growth and metastasis will not only deepen our understanding of the molecular mechanisms involved in tumor growth and metastasis, but also facilitate the use of Slit2 and Robo1 as the novel molecular targets of diagnosis and treatment of cancers.